The goal of this project is to develop AIDS-targeted drugs. A basic oligonucleoside phosphorothioates were synthesized and evaluated for their ability to (i) inhibit the replication of the virus in a de novo infection assay and (ii) inhibit HIV-1 reverse transcriptase. They were found to be potent inhibitors of reverse transcriptase, but poor inhibitors of de novo viral infection. Acyloxyalkyl esters of foscarnet were evaluated for their ability to function as suitable pro-drug forms of foscarnet. They were relatively poor pro-drugs; reasons for being poor pro-drugs were found to reside in their unfavorable hydrolytic characteristics. A variety of base- modified oligonucleoside phosphorothioates were synthesized and evaluated for their ability to function as potential improved anti-sense constructs (relative to a previously published sequence targeted to the rev-gene product). These sequences, wherein 5-F, 5-Cl, and 5-Br Uracil was substituted for thymidine, were not found to be superior.